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  1. Article ; Online: Theophylline Attenuates BLM-Induced Pulmonary Fibrosis by Inhibiting Th17 Differentiation.

    Park, Soo-Jin / Hahn, Hwa-Jeong / Oh, Sei-Ryang / Lee, Hyun-Jun

    International journal of molecular sciences

    2023  Volume 24, Issue 2

    Abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic and refractory interstitial lung disease. Although there are two approved drugs for IPF, they were not able to completely cure the disease. Therefore, the development of new drugs is required for the ... ...

    Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic and refractory interstitial lung disease. Although there are two approved drugs for IPF, they were not able to completely cure the disease. Therefore, the development of new drugs is required for the effective treatment of IPF. In this study, we investigated the effect of theophylline, which has long been used for the treatment of asthma, on pulmonary fibrosis. The administration of theophylline attenuated the fibrotic changes of lung tissues and improved mechanical pulmonary functions in bleomycin (BLM)-induced pulmonary fibrosis. Theophylline treatment suppressed IL-17 production through inhibiting cytokines controlling Th17 differentiation; TGF-β, IL-6, IL-1β, and IL-23. The inhibition of IL-6 and IL-1β by theophylline is mediated by suppressing BLM-induced ROS production and NF-κB activation in epithelial cells. We further demonstrated that theophylline inhibited TGF-β-induced epithelial-to-mesenchymal transition in epithelial cells through suppressing the phosphorylation of Smad2/3 and AKT. The inhibitory effects of theophylline on the phosphorylation of Smad2/3 and AKT were recapitulated in BLM-treated lung tissues. Taken together, these results demonstrated that theophylline prevents pulmonary fibrosis by inhibiting Th17 differentiation and TGF-β signaling.
    MeSH term(s) Animals ; Mice ; Bleomycin/toxicity ; Theophylline/pharmacology ; Interleukin-6/pharmacology ; Proto-Oncogene Proteins c-akt ; Lung ; Cell Differentiation ; Transforming Growth Factor beta/pharmacology ; Idiopathic Pulmonary Fibrosis/chemically induced ; Idiopathic Pulmonary Fibrosis/drug therapy ; Mice, Inbred C57BL
    Chemical Substances Bleomycin (11056-06-7) ; Theophylline (C137DTR5RG) ; Interleukin-6 ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Transforming Growth Factor beta
    Language English
    Publishing date 2023-01-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24021019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Daphnetin Alleviates Bleomycin-Induced Pulmonary Fibrosis through Inhibition of Epithelial-to-Mesenchymal Transition and IL-17A.

    Park, Soo-Jin / Ryu, Hyung Won / Kim, Ji-Hyeong / Hahn, Hwa-Jeong / Jang, Hyun-Jae / Ko, Sung-Kyun / Oh, Sei-Ryang / Lee, Hyun-Jun

    Cells

    2023  Volume 12, Issue 24

    Abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic and refractory interstitial lung disease. Although there is no cure for IPF, the development of drugs with improved efficacy in the treatment of IPF is required. Daphnetin, a natural coumarin derivative, ... ...

    Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic and refractory interstitial lung disease. Although there is no cure for IPF, the development of drugs with improved efficacy in the treatment of IPF is required. Daphnetin, a natural coumarin derivative, has immunosuppressive, anti-inflammatory, and antioxidant activities. However, its antifibrotic effects have not yet been elucidated. In this study, we investigated the antifibrotic effects of daphnetin on pulmonary fibrosis and the associated molecular mechanism. We examined the effects of daphnetin on splenocytes cultured in Th17 conditions, lung epithelial cells, and a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. We identified that daphnetin inhibited IL-17A production in developing Th17 cells. We also found that daphnetin suppressed epithelial-to-mesenchymal transition (EMT) in TGF-β-treated BEAS2B cells through the regulation of AKT phosphorylation. In BLM-treated mice, the oral administration of daphnetin attenuated lung histopathology and improved lung mechanical functions. Our findings clearly demonstrated that daphnetin inhibited IL-17A and EMT both in vitro and in vivo, thereby protecting against BLM-induced pulmonary fibrosis. Taken together, these results suggest that daphnetin has potent therapeutic effects on lung fibrosis by modulating both Th17 differentiation and the TGF-β signaling pathway, and we thus expect daphnetin to be a drug candidate for the treatment of IPF.
    MeSH term(s) Mice ; Animals ; Bleomycin/adverse effects ; Interleukin-17/metabolism ; Idiopathic Pulmonary Fibrosis/chemically induced ; Idiopathic Pulmonary Fibrosis/drug therapy ; Transforming Growth Factor beta/metabolism
    Chemical Substances daphnetin (XC84571RD2) ; Bleomycin (11056-06-7) ; Interleukin-17 ; Transforming Growth Factor beta
    Language English
    Publishing date 2023-12-08
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12242795
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Biodegradable PAMAM ester for enhanced transfection efficiency with low cytotoxicity.

    Nam, Hye Yeong / Nam, Kihoon / Hahn, Hwa Jeong / Kim, Bo Hye / Lim, Hyun Jung / Kim, Hyun Jin / Choi, Joon Sig / Park, Jong-Sang

    Biomaterials

    2009  Volume 30, Issue 4, Page(s) 665–673

    Abstract: We synthesized biodegradable polycationic PAMAM (polyamidoamine) esters (e-PAM-R, e-PAM-K) that contain arginines or lysines at the peripheral ends of PAMAM-OH dendrimer through ester bond linkages. The PAMAM esters were readily degradable under ... ...

    Abstract We synthesized biodegradable polycationic PAMAM (polyamidoamine) esters (e-PAM-R, e-PAM-K) that contain arginines or lysines at the peripheral ends of PAMAM-OH dendrimer through ester bond linkages. The PAMAM esters were readily degradable under physiological conditions (pH 7.4, 37 degrees C), with more than 50% of the grafted amino acids hydrolyzed within 5h. However, polyplexes were very stable and were hardly degraded in the endosomal pH range. Moreover, these amino-acid-modified polymers showed excellent buffering capacities between pH 5.1 and 7.4, facilitating endosomal escape of polyplexes. While the lysine-grafted PAMAM ester did not display significant improvement in transfection efficiency, the arginine-conjugated PAMAM ester-mediated transfection of a luciferase gene showed better transfection efficiency than the branched 25 kDa PEI (polyethylenimine) and PAM-R (peptide bond), and lower cytotoxicity, especially with primary cells such as HUVECs (human umbilical vein endothelial cells) and SMCs (primary rat aorta vascular smooth muscle cells). Furthermore, after DNA release, free e-PAM-R degraded completely into nontoxic PAMAM-OH and arginines by hydrolysis, which resulted in lower cytotoxicity in contrast to the poorly degradable arginine-modified PAMAM with amide bonds. These findings demonstrated that the arginine-grafted biodegradable PAMAM dendrimer, e-PAM-R, is a potential candidate as a safe and efficient gene delivery carrier for gene therapy.
    MeSH term(s) Animals ; Arginine ; Buffers ; Cell Death/drug effects ; Cell Line ; Dendrimers ; Electrophoresis, Agar Gel ; Esters/chemical synthesis ; Esters/chemistry ; Esters/pharmacology ; Humans ; Lysine ; Microscopy, Confocal ; Plasmids/metabolism ; Polyamines/chemical synthesis ; Polyamines/chemistry ; Polyamines/pharmacology ; Polymers ; Rats ; Titrimetry ; Transfection
    Chemical Substances Buffers ; Dendrimers ; Esters ; PAMAM Starburst ; Polyamines ; Polymers ; Arginine (94ZLA3W45F) ; Lysine (K3Z4F929H6)
    Language English
    Publishing date 2009-02
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2008.10.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 2371: Show issues Location:
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  4. Article: Evaluation of generations 2, 3 and 4 arginine modified PAMAM dendrimers for gene delivery.

    Nam, Hye Yeong / Hahn, Hwa Jeong / Nam, Kihoon / Choi, Woo-Hyung / Jeong, Yunseong / Kim, Dong-Eun / Park, Jong-Sang

    International journal of pharmaceutics

    2008  Volume 363, Issue 1-2, Page(s) 199–205

    Abstract: It is a matter of concern to develop and design synthetic non-viral gene carriers with high transfection efficiency and low cytotoxicity in gene therapy. Recently, various arginine conjugated dendrimers showed better performance in transfection and ... ...

    Abstract It is a matter of concern to develop and design synthetic non-viral gene carriers with high transfection efficiency and low cytotoxicity in gene therapy. Recently, various arginine conjugated dendrimers showed better performance in transfection and greater viability than polyethyleneimine (PEI). In this study, we synthesized and investigated e-PAM-R G2, 3 and 4 which are biodegradable polyamidoamine (PAMAM) dendrimers modified with arginine and compared that with PAMAM-R series containing amide bonds for gene carriers. For plasmid DNA delivery, the transfection efficiency of e-PAM-R G4 was higher than G3 and G2 and similar to PAMAM-R G4 with favorable cell viability. Moreover, they indicated significantly higher suppression of TEL/AML1 protein, maybe due to rapid olidonucleotide (ODNs) release through biodegradability of e-PAM-R. These results suggest that biodegradable and non-toxic e-PAM-R may be useful carriers for the gene including plasmid DNA, antisense ODNs and si-RNA.
    MeSH term(s) Active Transport, Cell Nucleus ; Arginine/analogs & derivatives ; Arginine/chemical synthesis ; Arginine/metabolism ; Arginine/toxicity ; Artificial Gene Fusion ; Cell Nucleus/metabolism ; Cell Survival/drug effects ; Cells, Cultured ; Core Binding Factor Alpha 2 Subunit/genetics ; Core Binding Factor Alpha 2 Subunit/metabolism ; DNA/chemistry ; DNA/metabolism ; DNA, Catalytic/genetics ; DNA, Catalytic/metabolism ; Dendrimers ; Dose-Response Relationship, Drug ; Down-Regulation ; Humans ; Hydrolysis ; Magnetic Resonance Spectroscopy ; Oligonucleotides, Antisense/metabolism ; Polyamines/chemical synthesis ; Polyamines/metabolism ; Polyamines/toxicity ; Proto-Oncogene Proteins c-ets/genetics ; Proto-Oncogene Proteins c-ets/metabolism ; RNA, Small Interfering/metabolism ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Time Factors ; Transfection ; ETS Translocation Variant 6 Protein
    Chemical Substances Core Binding Factor Alpha 2 Subunit ; DNA, Catalytic ; Dendrimers ; Oligonucleotides, Antisense ; PAMAM Starburst ; Polyamines ; Proto-Oncogene Proteins c-ets ; RNA, Small Interfering ; RUNX1 protein, human ; Repressor Proteins ; DNA (9007-49-2) ; Arginine (94ZLA3W45F)
    Language English
    Publishing date 2008-07-30
    Publishing country Netherlands
    Document type Comparative Study ; Journal Article
    ZDB-ID 428962-6
    ISSN 1873-3476 ; 0378-5173
    ISSN (online) 1873-3476
    ISSN 0378-5173
    DOI 10.1016/j.ijpharm.2008.07.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1409: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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